Kidd T, Bland K S, Goodman C S
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Cell. 1999 Mar 19;96(6):785-94. doi: 10.1016/s0092-8674(00)80589-9.
Previous studies suggested that Roundabout (Robo) is a repulsive guidance receptor on growth cones that binds to an unknown midline ligand. Here we present genetic evidence that Slit is the midline Robo ligand; a companion paper presents biochemical evidence that Slit binds Robo. Slit is a large extracellular matrix protein expressed by midline glia. In slit mutants, growth cones enter the midline but never leave it; they abnormally continue to express high levels of Robo while at the midline. slit and robo display dosage-sensitive genetic interactions, indicating that they function in the same pathway. slit is also required for migration of muscle precursors away from the midline. Slit appears to function as a short-range repellent controlling axon crossing of the midline and as a long-range chemorepellent controlling mesoderm migration away from the midline.
先前的研究表明，Roundabout（Robo）是生长锥上的一种排斥性导向受体，它与一种未知的中线配体结合。在此我们提供遗传学证据表明，Slit是中线Robo配体；一篇配套论文提供了生化证据表明Slit与Robo结合。Slit是一种由中线神经胶质细胞表达的大型细胞外基质蛋白。在slit突变体中，生长锥进入中线但从未离开；它们在中线时异常地持续高水平表达Robo。slit和robo表现出剂量敏感的遗传相互作用，表明它们在同一途径中发挥作用。Slit对于肌肉前体细胞从中线迁移也是必需的。Slit似乎作为一种短程排斥因子控制轴突穿过中线，并作为一种长程化学排斥因子控制中胚层从中线迁移。
